Preliminary report of Iranian Registry of Alzheimer's disease in Tehran province: A cross‐sectional study in Iran

Abstract Background and Aims Alzheimer's disease (AD) is the main cause of dementia and over the 55 million people live with dementia worldwide. We aimed to establish the first database called the Iranian Alzheimer's Disease Registry to create a powerful source for future research in the country. In this report, the design and early results of the Iranian Alzheimer's Disease Registry will be described. Methods We performed this multicenter investigation and patients' data including age, sex, educational level, disease status, Mini‐Mental State Examination (MMSE), and Geriatric Depression Scale (GDS) from 2018 to 2021 were collected, registered, and analyzed by GraphPad Prism software. Results Totally 200 AD patients were registered in our database. 107 (54%) were women and age of 147 (74%) were over 65. The mean age for men and women was 76.20 ± 8.29 and 76.40 ± 8.83 years, respectively. 132 (66%) were married and 64 (32%) were illiterate. Also, 94 (47%) were in the moderate stage of disease, and 150 (75%) lived at home together with their families. The most frequent neurological comorbidity was psychosis (n = 72, 36%), while hypertension was the most common non‐neurological comorbidity (n = 104, 52%). The GDS score of women in the mild stage (5.23 ± 2.9 vs. 6.9 ± 2.6, p = 0.005) and moderate stage (5.36 ± 2.4 vs. 8.21 ± 2.06, p = <0.001) of the disease was significantly greater than men. In univariate analysis, MMSC score was remarkably associated with stroke (β = −2.25, p = 0.03), psychosis (β = −2.18, p = 0.009), diabetes (β = 3.6, p = <0.001), and hypercholesteremia (β = 1.67, p = 0.05). Also, the MMSE score showed a notable relationship with stroke (β = −2.13, p = 0.05) and diabetes (β = 3.26, p = <0.001) in multivariate analysis. Conclusion Iranian Alzheimer's Disease Registry can provide epidemiological and clinical data to use for purposes such as enhancing the current AD management in clinical centers, filling the gaps in preventative care, and establishing effective monitoring and cure for the disease.

Results: Totally 200 AD patients were registered in our database. 107 (54%) were women and age of 147 (74%) were over 65. The mean age for men and women was 76.20 ± 8.29 and 76.40 ± 8.83 years, respectively. 132 (66%) were married and 64 (32%) were illiterate. Also, 94 (47%) were in the moderate stage of disease, and 150 (75%) lived at home together with their families. The most frequent neurological comorbidity was psychosis (n = 72, 36%), while hypertension was the most common non-neurological comorbidity (n = 104, 52%). The GDS score of women in the mild stage (5.23 ± 2.9 vs. 6.9 ± 2.6, p = 0.005) and moderate stage (5.36 ± 2.4 vs. 8.21 ± 2.06, p = <0.001) of the disease was significantly greater than men. In univariate analysis, MMSC score was remarkably associated with stroke (β = −2.25, Dementia is defined as a decline in cognitive function impairing a person's previous status of social and occupational function. AD is the most common type of dementia, whereas vascular dementia is the second. Other major types of diseases causing dementia are psychiatric disorders, frontotemporal dementia, and Lewy body dementia. 4 AD imposes a negative impact not only on the patients but also on their relatives, particularly those directly responsible for their care. A recent report from the World Health Organization (WHO) showed that neurological disorders, ranging from epilepsy to AD, traumatic brain injury (TBI), multiple sclerosis (MS), neuroinfections, stroke, and PD, affect up to one billion people across the world and dementia has been considered as one of the neurological diseases that encourages governments to provide support for caregivers. 5 Global estimated prevalence for dementia is 3.9% for people over 60, with the local prevalence being 4.0% in China and Western Pacific regions, 1.6% in Africa, 4.6% in Latin America, 6.4% in North America, and 5.4% in Western Europe. 6 World Alzheimer Report in 2021 released by Alzheimer Disease International (ADI) reported that over 55 million dementia people live in the world. This number will go up with an aging population to more than 78 million by 2030 in the world. 7 World Alzheimer Report has shown that major barriers to AD and dementia diagnosis in people and caregivers include lack of access to experienced clinicians (47%), fear of diagnosis (46%), and cost (34%). 8 Most of the people with AD and their family carers feel isolated in society and lose their friends and even family members. 9 Surgeon General of the US Public Health Service established the National Committee on Vital and Health Statistics (NCVHS) in 1949. 10 NCVHS introduced registries as an organized system for the gathering, storage, retrieval, processing, and spread of data to individuals with certain disorders or conditions that put them at risk of a health-related event or adverse health effects. 11

| Clinical assessment of AD
Experienced neurologists and neuropsychiatrists examined all patients through past medical history, clinical examination, neuropsychological evaluation, laboratory tests, and neuroimaging. Also, further assessment was performed to evaluate memory deficit and other thinking abilities, quality of the judge, and identify changes in behavior to determine stages of AD and comorbidities based on the International Classification of Diseases, 10th Revision (ICD-10). 15 AD is classified into mild, moderate, and severe stages in terms of Clinical Dementia Rating (CDR) which is a global dementia rating scale to evaluate cognitive change, identify the presence of dementia, and determine severity of dementia from very mild (CDR 0.5) to mild (CDR 1), moderate (CDR 2), and severe (CDR 3). 16 In mild disease, patients experience some functional dependence, such as trouble managing finances. In the moderate form of the disease, patients are more dependent on others, have difficulty with bathing and shopping, and often are not able to drive. The severe form is characterized by total dependence on care providers and deficit in motor and balance. 17

| Assessment of comorbidities
Neurological comorbidities were investigated through brain magnetic resonance imaging (MRI) and computed tomography (CT) to detect brain ischemia due to transient ischemic attack or mild ischemic stroke and small vessel disease. 18 Also, PD was diagnosed in the case of micrographia, visible resting tremor, hypomimia, slowed repetitive movements, impaired arm swing, and pain in muscles. 19 Patients with frequent extrapyramidal signs, more rapid cognitive dysfunction, and greater deficit in the putative neuropsychological examination of frontal lobe function were assessed for existing depression and psychosis as psychotic symptoms of AD. 20 For none neurological comorbidities, patients were considered diabetics if they had hemoglobin A1c ≥ 6.5%, nonfasting blood glucose ≥ 200 mg/dl, and fasting blood glucose ≥ 126 mg/ dl. 21 Hypertension in patients was diagnosed if blood pressure was consistently above130 and/or above 80 mmHg 22  questions is available to use in clinical practice more attractively, as it can considerably lower administration time. 27 We used the Persian version of GDS developed by Malakouti et al. 28 to reach the medical diagnosis of a major depressive episode in older people.

| Statistical analysis
Patients' data was stored in a database, namely Iranian collaborated AD, and then were transferred to the Iranian Alzheimer's Disease Registry. Identified AD cases were registered in the database and patient data were subsequently processed and analyzed using   Figure 1, indicating that the severe stage of disease was more evident in women than men (76% vs. 23%).
Regarding the assessment of cognitive status, there was no statistically notable difference between men and women for MMSE score in different stages of the disease, nevertheless, women got significantly higher GDS scores than men in the mild (5.23 ± 2.9 vs.
FAHANIK-BABAEI ET AL. | 5 of 8 executive function. 31 These neuropsychiatric symptoms, which are categorized as behavioral and psychological symptoms of dementia (BPSD), are prevalent and occur during the gradual progress of the disease. 32 In the first Iranian Alzheimer's Disease Registry, which was initiated in the province of Tehran in 2018, 45% of AD patients were in the mild stage of disease, 47% were moderate, and 8% were in the late stage of AD. Moreover, MMSE and GDS scores in women differed significantly between mild and moderate stage of AD. Also, the MMSE score was associated with neurological and none neurological comorbidities in AD patients. The gender-specific difference in the phenotype of AD is to be explained by differences in brain morphology and function as well as higher susceptibility for pathological lesions in women and also greater cognitive reserve in men. Sex differences have also been reported for the expression of antioxidative enzymes and post-menopausal hormonal changes. 33 Patient registries are strong tools to monitor the course of diseases, prevent and treat the diseases, and evaluate parameters that influence prognosis and quality of life. 34 Patient registries provide a comprehensive database, and therefore, generated data may be generalizable to a variety of patients. 35 The Iranian Alzheimer's Disease Registry generated information about patients with AD who were visited and consulted by neurologists and psychiatrists in outpatient clinics and medical centers for 2 years.
Our population contained more women than men (107 vs. 93) which is in parallel with other databases in the literature 15 and indicates a higher incidence of AD in women than in men. [36][37][38] ADI report calculates that globally 75% of dementia people are misdiagnosed and this figure may be as high as 90% in some lowand middle-income regions of the world, where lack of awareness of dementia remains a major barrier to AD diagnosis. 7 The World Alzheimer Report 2010 reported that the economic cost of dementia was USD 604 billion which was equal to 1% of the global gross domestic product. 39 Based on the ADI report, this figure showed an increase of 35% in 2015 and it is predicted that

CONFLICT OF INTEREST
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.

TRANSPARENCY STATEMENT
The lead author Mohsen Sedighi, Tourandokht Baluchnejadmojarad affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.